Interaction of dengue virus nonstructural protein 5 with Daxx modulates RANTES production

Khunchai, Sasiprapa; Junking, Mutita; Suttitheptumrong, Aroonroong; Yasamut, Umpa; Sawasdee, Nunghathai; Netsawang, Janjuree; Morchang, Atthapan; Chaowalit, Prapaipit; Noisakran, Sansanee; Yenchitsomanus, Pa‐thai; Limjindaporn, Thawornchai

doi:10.1016/j.bbrc.2012.05.137

Cited by 24 publications

(25 citation statements)

References 29 publications

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“…To investigate whether the RdRP activity of TBEV NS5 affects RANTES induction, we constructed and analyzed TBEV NS5 mutant D664A. It has been reported that in the absence of the functional nuclear localization signal, DENV NS5 could neither translocate into the nucleus nor interact with Daxx to increase RANTES production (51). The importin b-binding site (bipartite nuclear localization signal [bNLS]) is highly conserved among DENV and related flaviviruses (52).…”

Section: The Rdrp Activity Of Tbev Ns5 Is Important For Rantes Inductionmentioning

confidence: 99%

Tick-Borne Encephalitis Virus Nonstructural Protein NS5 Induces RANTES Expression Dependent on the RNA-Dependent RNA Polymerase Activity

Zheng

Yang

Jiang

et al. 2018

The Journal of Immunology

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Tick-borne encephalitis virus (TBEV) is one of the flaviviruses that targets the CNS and causes encephalitis in humans. The mechanism of TBEV that causes CNS destruction remains unclear. It has been reported that RANTES-mediated migration of human blood monocytes and T lymphocytes is specifically induced in the brain of mice infected with TBEV, which causes ensuing neuroinflammation and may contribute to brain destruction. However, the viral components responsible for RANTES induction and the underlying mechanisms remain to be fully addressed. In this study, we demonstrate that the NS5, but not other viral proteins of TBEV, induces RANTES production in human glioblastoma cell lines and primary astrocytes. TBEV NS5 appears to activate the IFN regulatory factor 3 (IRF-3) signaling pathway in a manner dependent on RIG-I/MDA5, which leads to the nuclear translocation of IRF-3 to bind with RANTES promoter. Further studies reveal that the activity of RNA-dependent RNA polymerase (RdRP) but not the RNA cap methyltransferase is critical for TBEV NS5-induced RANTES expression, and this is likely due to RdRP-mediated synthesis of dsRNA. Additional data indicate that the residues at K359, D361, and D664 of TBEV NS5 are critical for RdRP activity and RANTES induction. Of note, NS5s from other flaviviruses, including Japanese encephalitis virus, West Nile virus, Zika virus, and dengue virus, can also induce RANTES expression, suggesting the significance of NS5-induced RANTES expression in flavivirus pathogenesis. Our findings provide a foundation for further understanding how flaviviruses cause neuroinflammation and a potential viral target for intervention.

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Section: The Rdrp Activity Of Tbev Ns5 Is Important For Rantes Inductionmentioning

confidence: 99%

Tick-Borne Encephalitis Virus Nonstructural Protein NS5 Induces RANTES Expression Dependent on the RNA-Dependent RNA Polymerase Activity

Zheng

Yang

Jiang

et al. 2018

The Journal of Immunology

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“…Another study also showed that tumor necrosis factor α (TNF-α) expression was also up-regulated by NF-κB in presence of NS5 protein. The direct binding of NS5 to NF-κB has not been shown, but NS5 was proposed to bind to the Daxx protein [79], and compete with its interaction with NF-κB. This would lead to NF-κB release and its interaction with the RANTES promoter and the up-regulation of its expression.…”

Section: Host Interacting Partnersmentioning

confidence: 99%

Dengue Virus Non-Structural Protein 5

Sahili¹,

Lescar

2017

Viruses

112

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The World Health Organization estimates that the yearly number of dengue cases averages 390 million. This mosquito-borne virus disease is endemic in over 100 countries and will probably continue spreading, given the observed trend in global warming. So far, there is no antiviral drug available against dengue, but a vaccine has been recently marketed. Dengue virus also serves as a prototype for the study of other pathogenic flaviviruses that are emerging, like West Nile virus and Zika virus. Upon viral entry into the host cell and fusion of the viral lipid membrane with the endosomal membrane, the viral RNA is released and expressed as a polyprotein, that is then matured into three structural and seven non-structural (NS) proteins. The envelope, membrane and capsid proteins form the viral particle while NS1-NS2A-NS2B-NS3-NS4A-NS4B and NS5 assemble inside a cellular replication complex, which is embedded in endoplasmic reticulum (ER)-derived vesicles. In addition to their roles in RNA replication within the infected cell, NS proteins help the virus escape the host innate immunity and reshape the host-cell inner structure. This review focuses on recent progress in characterizing the structure and functions of NS5, a protein responsible for the replication and capping of viral RNA that represents a promising drug target.

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“…NS5 also interacts with death-domain-associate protein (Daxx), a transcription repressor shown to be important to induce expression of the cytokine RANTES [59]. In addition, the ability of NF-κB to bind RANTES promoter is increased in cells expressing NS5 [60], suggesting that NS5 may contribute to DENV pathogenesis by inducing increases of cytokine expression.…”

Section: Participation Of Denv Nsps In Dengue Physiopathologymentioning

confidence: 99%

Non-Canonical Roles of Dengue Virus Non-Structural Proteins

Zeidler

Fernandes-Siqueira

Barbosa

et al. 2017

Viruses

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The Flaviviridae family comprises a number of human pathogens, which, although sharing structural and functional features, cause diseases with very different outcomes. This can be explained by the plurality of functions exerted by the few proteins coded by viral genomes, with some of these functions shared among members of a same family, but others being unique for each virus species. These non-canonical functions probably have evolved independently and may serve as the base to the development of specific therapies for each of those diseases. Here it is discussed what is currently known about the non-canonical roles of dengue virus (DENV) non-structural proteins (NSPs), which may account for some of the effects specifically observed in DENV infection, but not in other members of the Flaviviridae family. This review explores how DENV NSPs contributes to the physiopathology of dengue, evasion from host immunity, metabolic changes, and redistribution of cellular components during infection.

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Interaction of dengue virus nonstructural protein 5 with Daxx modulates RANTES production

Cited by 24 publications

References 29 publications

Tick-Borne Encephalitis Virus Nonstructural Protein NS5 Induces RANTES Expression Dependent on the RNA-Dependent RNA Polymerase Activity

Tick-Borne Encephalitis Virus Nonstructural Protein NS5 Induces RANTES Expression Dependent on the RNA-Dependent RNA Polymerase Activity

Dengue Virus Non-Structural Protein 5

Non-Canonical Roles of Dengue Virus Non-Structural Proteins

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